Related Experiment Video
Updated: Mar 25, 2026
Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Novel somatic mutations identified by whole-exome sequencing in muscle-invasive transitional cell carcinoma of the
Huixing Pan1, Xiaojian Xu2, Deyao Wu3
1Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China; Department of Urology, The Fourth Affiliated Hospital of Nantong Medical College, Yancheng City No. 1 People's Hospital, Yancheng, Jiangsu 224006, P.R. China.
Abstract:
Transitional cell carcinoma (TCC) is the one of the most commonly observed types of cancer globally. The identification of novel disease-associated genes in TCC has had a significant effect on the diagnosis and treatment of bladder cancer; however, there may be a large number of novel genes that have not been identified. In the present study, the exomes of two individuals who were diagnosed with muscle-invasive TCC (MI-TCC) were sequenced to investigate potential variants. Subsequently, following algorithm and filter analysis, Sanger sequencing was used to validate the results of deep sequencing. Immunohistochemistry (IHC) was employed to observe the differences in HECT, C2 and WW domain-containing E3 ubiquitin protein ligase 1 (HECW1) protein expression between tumor tissues and para-carcinoma tissues. A total of 6 nonsynonymous mutation genes were identified in MI-TCC, identified as copine VII, RNA binding motif protein, X-linked-like 3, acyl-CoA synthetase medium-chain family member 2A, HECW1, zinc finger protein 273 and trichohyalin. Furthermore, 5 cases were identified to possess a HECW1 gene mutation in 61 MI-TCC specimens, and all of these were point mutations located at exon 11 on chromosome 7. The mutation categories of HECW1 had 4 missense mutations and 1 nonsense mutation. IHC revealed that HECW1 protein was expressed at significantly increased levels in MI-TCC compared with normal bladder urothelium (P<0.001). The present study provided a novel approach for investigating genetic changes in the MI-TCC exome, and identified the novel mutant gene HECW1, which may possess a significant role in the pathogenesis of TCC.
Insights
Researchers identified novel gene mutations in muscle-invasive transitional cell carcinoma (MI-TCC). The study found mutations in the HECT, C2 and WW domain-containing E3 ubiquitin protein ligase 1 (HECW1) gene, suggesting its role in bladder cancer development.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Transitional cell carcinoma (TCC) is a prevalent global cancer, with bladder cancer being a significant subset.
- Identifying novel genetic drivers is crucial for advancing TCC diagnosis and treatment.
- Previous research suggests numerous undiscovered genes may contribute to TCC pathogenesis.
Purpose of the Study:
- To investigate potential genetic variants in muscle-invasive TCC (MI-TCC) through exome sequencing.
- To identify novel genes implicated in the development of MI-TCC.
- To assess the expression levels of HECT, C2 and WW domain-containing E3 ubiquitin protein ligase 1 (HECW1) in MI-TCC.
Main Methods:
- Exome sequencing of two MI-TCC individuals.
- Bioinformatic analysis and filtering of sequencing data.
- Validation using Sanger sequencing.
- Immunohistochemistry (IHC) to evaluate HECW1 protein expression in tumor and adjacent tissues.
Main Results:
- Six nonsynonymous mutation genes were identified in MI-TCC.
- HECW1 gene mutations were found in 5 out of 61 MI-TCC specimens, specifically point mutations in exon 11.
- HECW1 protein expression was significantly elevated in MI-TCC tissues compared to normal bladder urothelium (P<0.001).
Conclusions:
- Exome sequencing offers a novel approach to uncover genetic alterations in MI-TCC.
- HECW1 is identified as a novel mutant gene potentially involved in TCC pathogenesis.
- Elevated HECW1 expression suggests its role in the progression of muscle-invasive bladder cancer.
Related Concept Videos
02:21Cancers Originate from Somatic Mutations in a Single Cell
02:21Cancers Originate from Somatic Mutations in a Single Cell